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Biomedical subjects

J Lindenfeld

Publications and source records attributed to J Lindenfeld.

36 records · Page 2Linked to original sources
PubMed1992

Hirudins: antithrombin anticoagulants.

OBJECTIVE: To review the chemistry, pharmacology, available clinical data, and adverse effects of the hirudin anticoagulants. DATA SOURCES: A MEDLINE search and a review of recent scientific abstracts was conducted to identify pertinent literature. STUDY SELECTION: Focus was placed on studies conducted in humans. Because hirudin is still an investigational agent, however, relevant animal data, particularly pharmacokinetic studies and studies of preclinical efficacy, were also selected. DATA EXTRACTION: Data from both human and animal studies were evaluated; emphasis was placed on human trials. DATA SYNTHESIS: Hirudin has demonstrated potent anticoagulant effects. Although hirudin could have a significant impact on the therapeutic management of patients requiring anticoagulant therapy, only a limited number of human studies have been published to date. Trials comparing hirudin and heparin in specific patient populations are still ongoing. CONCLUSIONS: Although still in clinical trials, hirudin is a unique agent that may represent a breakthrough in anticoagulant therapy. The specific role that this agent will play in the management of patients has yet to be determined.

Amino Acid Sequence↗
PubMed1990

Successful treatment of sarcoidosis-associated pulmonary hypertension with corticosteroids.

We report a case of sarcoidosis presenting with cor pulmonale of a greater severity than would be expected from the degree of hypoxia and pulmonary fibrosis. Right heart catheterization revealed that mean pulmonary artery pressure was markedly increased (42 mm Hg), was not reduced by supplemental oxygen, but was reduced significantly (25 mm Hg) after 16 weeks of therapy with corticosteroids. Improvement in symptoms and pulmonary function was maintained for an 18-month period of observation after cessation of corticosteroid therapy.

Adult↗
PubMed1989

Effects of ventricular fibrillation and defibrillation on pacing threshold in the anesthetized dog.

The effects of transthoracic and internal defibrillation on the bipolar ventricular pacing threshold in 20 anesthetized dogs were examined. Ventricular pacing was accomplished with a computer-controlled, constant voltage pacemaker that permitted rapid determination of pacing threshold. Defibrillation at various energy levels was administered during ventricular pacing and after ventricular fibrillation of 5, 15, 30, 45, 60 or 120 s duration in the 20 dogs. Defibrillation during pacing or within 15 s after initiation of ventricular fibrillation did not significantly increase threshold, regardless of defibrillation energy or mode of delivery. Defibrillation after ventricular fibrillation lasting greater than or equal to 30 s increased (p less than 0.05) threshold determined 6 s after defibrillation. The increase in threshold (in volts) determined 6 s after defibrillation was an exponential function of fibrillation duration (30 s = 0.30 +/- 0.09 V; 45 s = 0.53 +/- 0.13 V; 60 s = 2.24 +/- 1.05 V), but was independent of defibrillation energy or mode of delivery. Threshold returned to control values 15 to 30 s after defibrillation. Cardiopulmonary bypass to maintain coronary perfusion prevented the increase in pacing threshold even after ventricular fibrillation of up to 2 min duration. Pacing threshold is not increased by transthoracic or internal defibrillation, but is increased by ventricular fibrillation of sufficient duration to create substantial myocardial hypoxemia.

Anesthesia↗
PubMed1988

Effects of chronic beta-adrenergic blockade on exercise training in dogs.

To assess the role of beta-adrenergic stimulation in cardiovascular conditioning we examined the effects of a beta-adrenergic blocker, propranolol, in mongrel dogs during an 8-wk treadmill-training program. Seven dogs were trained without a drug (NP), six were trained on propranolol 10 mg.kg-1.day-1 (P), and five served as caged controls (C). Effective beta-adrenergic blockade was documented by a decrease in peak exercise heart rate of 54 +/- 11 (SE) beats/min (P less than 0.05) and a one-log magnitude of increase in the isoproterenol-heart rate dose-response curve. Testing was performed before drug treatment or training and again after training without the drug for 5 days. Submaximal exercise heart rate decreased similarly in both NP and P (-26 +/- 4 NP vs. -25 +/- 9 beats/min P, P less than 0.05 for both) but peak heart rate decreased only with NP (-33 +/- 9 beats/min, P less than 0.05). Treadmill exercise time increased similarly in both groups: 3.4 +/- 0.6 min in NP and 3.0 +/- 0.2 min in P (both P less than 0.05). Blood volume also increased after training in both groups: 605 +/- 250 ml (26%) in NP and 377 +/- 140 ml (17%) in P (both P less than 0.05). Submaximal exercise arterial lactates were reduced similarly in both groups but peak exercise lactate was reduced more in NP (-1.4 +/- 0.3 NP vs -0.3 +/- 0.12 mmol/l P, P less than 0.05). Lactate threshold increased in both groups but the increase was greater in NP (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Failure of epinephrine to improve the balance between myocardial oxygen supply and demand during closed-chest resuscitation in dogs.

Although large doses of epinephrine increase coronary perfusion pressure and flow during cardiopulmonary resuscitation, epinephrine also increases myocardial oxygen consumption during ventricular fibrillation. To test the hypothesis that epinephrine improves the balance between myocardial oxygen supply and demand during cardiopulmonary resuscitation, myocardial adenosine 5'-triphosphate (ATP) and lactate concentrations were measured before and immediately after 10 minutes of cardiopulmonary resuscitation in 10 control dogs and 10 dogs given intravenous epinephrine (1-mg bolus followed by 0.2 mg/min). Left ventricular myocardial blood flow during cardiopulmonary resuscitation was measured with radioactive microspheres and was significantly higher in the epinephrine group (48 +/- 11 vs. 21 +/- 4 ml/min/100 g, p less than 0.05). However, myocardial lactate concentration increased significantly (p less than 0.01) after cardiopulmonary resuscitation in both groups and tended to increase more in epinephrine-treated animals. Myocardial ATP concentration decreased significantly (p less than 0.05) and by comparable amounts in the two groups. These findings suggest that large doses of epinephrine may fail to improve the balance between myocardial oxygen supply and demand during cardiopulmonary resuscitation, even when they result in a substantial increase in coronary blood flow.

Adenosine Triphosphate↗
PubMed1985

Effects of enhanced ventricular filling on cardiac pump performance in exercising dogs.

The extent to which the normal increase in stroke volume during exercise can be augmented by increasing preload by dextran infusion was studied in seven dogs. Each dog ran 3 min on a level treadmill at mild (3-4 mph), moderate (6-8 mph), and severe (9-13 mph) loads during the control study and immediately after 10% dextran 14 ml/kg iv. During severe exercise dextran-augmented stroke volume (+5.4 ml or 19% vs. exercise without dextran, P less than 0.01) and left ventricular end-diastolic diameter and pressure did not change heart rate, aortic pressure, or maximum derivative of left ventricular pressure but decreased systemic vascular resistance by 16%. Similar increases in stroke volume and preload after dextran occurred during mild and moderate exercise when arterial pressure and heart rate were unchanged or increased and systemic vascular resistance was decreased. Thus altering preload above those levels normally encountered during exercise is a potential mechanism to increase stroke volume and cardiac output.

Animals↗
PubMed1985

A potential method of correcting intracavitary left ventricular filling pressures for the effects of positive end-expiratory airway pressure.

Based on the observation that positive end-expiratory airway pressure (PEEP) causes comparable increments in intrapericardial and right-sided intracardiac pressures, we hypothesized that intracavitary left ventricular filling pressures measured in the presence of PEEP can be corrected for increased intrathoracic pressure by subtracting the effects of PEEP on intracavitary right ventricular filling pressures. Ventricular function curves (aortic blood flow vs intracavitary left ventricular end-diastolic pressure [LVEDP]) were generated with and without 15 cm of water of PEEP in eight dogs. All curves were shifted to the right by PEEP (i.e., intracavitary LVEDP was higher for any submaximal level of aortic blood flow). However, when pressures measured in the presence of PEEP were "corrected" by subtracting the corresponding increment in intracavitary right ventricular end-diastolic pressure caused by PEEP at each level of ventricular filling, control and corrected PEEP data points appeared to fall on the same curve in five dogs, and differed only slightly in three dogs. Mean control and corrected PEEP curves derived by averaging polynomial regression coefficients for each condition differed significantly from uncorrected PEEP curves (p less than .05), but not from each other. Analogous curves based on mean left atrial pressure were corrected equally well by subtracting the effects of PEEP on mean right atrial pressure. We conclude that the increments in intracavitary right heart filling pressures caused by PEEP can be used to correct intracavitary left heart filling pressures for the effects of PEEP on intrathoracic pressure.

Animals↗
PubMed1985

Hemodynamic response to normovolemic polycythemia at rest and during exercise in dogs.

Very little is known about the influence of polycythemia on oxygen transport during exercise. We studied chronically instrumented dogs trained to run on a treadmill before and after their hematocrit had been increased by isovolemic exchange transfusion with packed red blood cells. With normovolemic polycythemia, cardiac output fell in a linear fashion as hematocrit was increased to 65%, but these changes were balanced by an increasing oxygen content resulting in constant systemic oxygen transport. Oxygen consumption was unchanged both at rest and during exercise after induction of polycythemia. To investigate the effect of polycythemia on oxygen transport further, we measured both mixed venous Po2 and lactate. Mixed venous Po2 increased and lactate remained unchanged both at rest and in exercising polycythemic dogs. Thus, we conclude that, in conscious animals, systemic oxygen transport is well preserved with increasing hematocrit to at least 65%.

Animals↗
PubMed1984

Left ventricular platelet deposition after acute myocardial infarction. An attempt at quantification using blood pool subtracted indium-111 platelet scintigraphy.

Since indium-111 platelet scintigraphy for the detection of left ventricular thrombosis often shows considerable non-specific blood pool activity a subtraction method using simultaneous technetium-99m blood pool scintigraphy was undertaken in 11 subjects with well documented remote myocardial infarction, who served as positive or negative controls, and in 18 consecutive patients with acute myocardial infarction. The results were compared with those of cross sectional echocardiography. Thirteen patients had transmural myocardial infarction and the calculated count per pixel in the left ventricle of the subtracted indium-111 platelet scintigram was (mean (SD)) 0.28(0.35), but five patients with subendocardial myocardial infarction had a mean count of 0.04(0.06). In seven patients with transmural myocardial infarction (two anterior and five inferior) left ventricular thrombosis was detected by indium-111 platelet scintigraphy but in only one of these by cross sectional echocardiography. None of the patients with subendocardial myocardial infarction had left ventricular thrombosis. Subtracted left ventricular counts correlated well with the visual results. It is concluded that left ventricular platelet sequestration after acute myocardial infarction may be quantified and precisely located and that quantitative longitudinal studies of the natural history and drug intervention are now possible.

Adult↗
PubMed1984

Potential adverse effects of volume loading on perfusion of vital organs during closed-chest resuscitation.

To determine whether expansion of blood volume improves vital organ perfusion pressures and blood flow during closed-chest cardiopulmonary resuscitation in dogs, we recorded intracranial and high-fidelity ascending aortic and right atrial pressures and measured total and regional blood flow with radioactive microspheres during cardiopulmonary resuscitation before and after rapid infusion of 1 liter of saline or dextran in 12 animals. Volume loading increased total forward blood flow from 327.1 +/- 50.9 to 692.7 +/- 105.9 ml/min (p less than .01). However, blood flow to the cerebral hemispheres, cerebellum, brainstem, and ventricular myocardium all decreased significantly. For example, blood flow to the left cerebral hemisphere fell from 16.5 +/- 2.4 to 5.5 +/- 1.7 ml/min/100 g (p less than .001), while left ventricular myocardial blood flow fell from 12.0 +/- 3.1 to 4.1 +/- 0.8 ml/min/100 g (p less than .05). These changes in critical regional flow were accompanied by disproportionate increases in right atrial and intracranial pressures (relative to aortic pressure), which reduced the average pressure differences generated across the coronary and cerebral circulations from 11.0 +/- 2.5 to 3.7 +/- 1.3 mm Hg (p less than .01) and from 16.1 +/- 2.3 to 10.5 +/- 1.5 mm Hg (p less than .01), respectively. The overall rise in forward flow was associated with a marked increase in extracranial, brachiocephalic blood flow. These findings suggest that large increments in blood volume can reduce vital organ perfusion during cardiopulmonary resuscitation despite an increase in total forward blood flow.

Animals↗
PubMed1983

Low exercise pulmonary resistance is not dependent on vasodilator prostaglandins.

In resting conscious dogs, administration of cyclooxygenase inhibitors results in modest increases in pulmonary arterial pressure and pulmonary vascular resistance, suggesting that vasodilator prostaglandins play a role in maintaining the low vascular resistance in the pulmonary bed. To assess the role of these vasodilator prostaglandins on pulmonary vascular resistance during exercise, we studied seven mongrel dogs at rest and during exercise before and after intravenous meclofenamate (5 mg/kg). Following meclofenamate, pulmonary vascular resistance rose both at rest (250 24 vs. 300 +/- 27 dyn . s . cm-5, P less than 0.01) and with exercise (190 +/- 9 vs. 210 +/- 12 dyn . s . cm-5, P less than 0.05). Systemic vascular resistance rose slightly following meclofenamate both at rest and during exercise. There were no changes in cardiac output. The effects of cyclooxygenase inhibition, although significant, were less during exercise than at rest. This suggests that the normal fall in pulmonary vascular resistance during exercise depends largely on factors other than vasodilator prostaglandins.

Animals↗
PubMed1981

Increased plasma concentrations of platelet factor 4 in coronary artery disease: a measure of in vivo platelet activation and secretion.

Previous studies have shown that there is both a significant shortening in platelet survival and a measured hyperactivity to platelet-aggregating agents in patients with documented coronary artery disease compared with control groups. We used a recently described radioimmunoassay for the platelet-secreted protein platelet factor 4 (PF4) to study 162 patients with documented coronary artery disease. There was a significant increase in plasma PF4 concentrations in patients with documented coronary artery disease compared with angiographically normal patients (8.7 vs 16 ng/ml, respectively, n = 121), but as in previous studies of platelet survival, we could not correlate elevated plasma PF4 concentration and the severity or site of the coronary artery disease. In addition, there was no correlation with left ventricular function, serum cholesterol or the type of angina. Patients with confirmed acute myocardial infarction had no significant difference in mean plasma PF4 concentrations compared with similar groups of coronary disease patients who had prolonged chest pain or chronic stable angina. Coronary artery bypass grafting in a subgroup of patients did not affect the mean plasma PF4 concentration during 1 year of follow-up after bypass surgery, but medical therapy for angina with increasing doses of propranolol and nitrates significantly reduced PF4 concentration in another subgroup of patients who were not considered to be candidates for surgical therapy.

Angina Pectoris↗
PubMed1980

Effects of oral propranolol on left ventricular size and performance during exercise and acute pressure loading.

Oral propranolol (160 mg/day) was administered to 19 normal subjects for 2 weeks. Echocardiograms were performed at rest, during graded supine bicycle exercise in 10 subjects and during acute pressure loading with intravenous phenylephrine in the remaining nine subjects. Resting heart rate on propranolol decreased compared with control (52 +/- 8 vs 63 +/- 10 beats/min; p less than 0.001), as did systolic blood pressure (99 +/- 9 vs 107 +/- 9 mm Hg; p less than 0.01). Left ventricular end-diastolic dimension was slightly enlarged (48.3 +/- 4.2 vs 47.1 +/- 3.6 mm, p = 0.05), but percent dimensional shortening was unchanged (37 +/- 4 vs 38 +/- 5%). At each stage during supine bicycle exercise, heart rate was slower, blood pressure lower, left ventricular dimensions were larger and percent dimensional shortening was reduced on propranolol by an analysis of variance. In contrast, during acute pressure loading, while the heart rate response to increased blood pressure was blocked by atropine, there was no significant difference in left ventricle size and performance compared with control. We conclude that prolonged oral propranolol therapy has little, if any, intrinsic effect on myocardial performance in normal subjects. Its major action on the heart is competitive inhibition of beta-adrenergic tone, which is most manifest during conditions associated with increased sympathetic tone, such as exercise.

Adult↗
PubMed1980

Adrenergic responsiveness after abrupt propranolol withdrawal in normal subjects and in patients with angina pectoris.

Adrenergic responsiveness after abrupt propranolol withdrawas during exogenous and esdogenous catecholamine stimulation was assessed in 10 normal subjects and 10 patients with angina pectoris. Propranolol, 160 mg/day, was administered for 2 weeks and then stopped. During an epinephrine infusion, period (p < 0.005). There were no differences from control 96 hours after the drug had been stopped in both groups or at 144 hours in the angina patients who were studied for a longer time. At 48 hours of heart rate and the pressure-rate product were significantly less than control level in the angina patient, but not in the normal subjects. Similar results were observed during exercise in both groups. The epinephrine-induced increase in free fatty acids was blocked by propranolol (p < 0.005), was still attenuated at 48 hours of withdrawals (p < 0.05), but returned to control levels thereafter in both groups. Resting serum triiodothyromine levels decreased with propranolol ( < 0.005) and remaind low throughout the withdrawal period. Measurements of dopamine beta-hydroxylase, plasma platelet factor 4, and platelet aggregation at rest and after exercise did not change significantly during or after propranolol administration. Plasma norepinephrine and epinephrine values were not changed from control during the withdrawal period at rest or after exerise. We conclude that there is no evidence of hypersensitivity to beta-adrenergically mediated responses after abrupt propranolol withdrawal.

Adult↗
PubMedDate not supplied

Effects of amitriptyline on left ventricular function in conscious dogs.

Amitriptyline (Am) is a frequently prescribed tricyclic antidepressant drug associated with an increased risk of sudden death that has been presumed to be arrhythmia related. Little has been known about the effects of Am on left ventricular function. We studied i.v. Am (0.5, 1.0, and 1.5 mg/kg) in 10 conscious, resting, chronically instrumented dogs. Heart rate (HR) increased up to 70%; this increase was only partially prevented by propranolol. Left ventricular end diastolic pressure (LVEDP) decreased without, but not with, propranolol. Mean arterial pressure (MAP) increased by 10-13% transiently. The maximum rate of rise of left ventricular pressure (dP/dtmax) decreased by 16-18% without propranolol and by 14-29% with propranolol, indicating a moderate decrease in myocardial contractility. Changes in stroke volume were similar to changes in dP/dt. Thus, i.v. Am, at levels similar to therapeutic blood levels, causes a moderate depression of myocardial contractility, which is accentuated by propranolol. Tricyclic antidepressants, therefore, could have adverse effects on cardiac performance in patients with underlying myocardial dysfunction.

Amitriptyline↗